It has been postulated that brain and behavior affect the immune system and there is now a growing consensus in the literature that this effect is principally on the cell-mediated immune (CMI) system. Work in progress in this laboratory has been directed at testing the hypothesis that brain dopamine (DA) is related to CMI. The approach to the problem has been essentially pharmacologic, using dopamine receptor agonists and antagonists. The model for testing the CMI system depends upon a delayed-type hypersensitivity (DTH) to 2, 4-dinitrochlorobenzene (DNCB) in 2 month old C57BL/6 mice, possessing a functional immune system, and in 24-30 month old mice of the same strain which have a diminished (naturally suppressed) CMI system. Data collected thus far suggest that the timing of administration of DA receptor agonists and antagonists in vivo is critical to the observed DTH response. For instance, administration of haloperidol over a wide dosage range has no effect on the DTH response, when this drug is administered during the efferent arm of the immune response. Conversely, haloperidol at low doses (0.5 mg/kg) can either potentiate or suppress the DTH response, depending upon the timing of the administration of this drug in relationship to the afferent arm of the immune response. Evidence to date supports the notion that these in vivo drug effects are acting through the brain rather than through a direct action on lymphocytes.